Oral administration form comprising probiotic bacteria

ABSTRACT

The invention relates to an oral administration form which comprises at least one species of probiotic microorganisms, where it itself and/or the probiotic bacteria is/are provided with a coating which comprises at least two cellulose ethers.

The invention relates to an oral administration form which comprises atleast one species of probiotic microorganisms, where it itself and/orthe probiotic bacteria is/are provided with a coating which comprises atleast two cellulose ethers.

Probiotic microorganisms are already employed diversely today in theform of selected foods, food supplement preparations or medicaments inorder to amelio-rate or eliminate symptoms which causes disturbed ordamaged intestinal flora. One problem is the high loss of activity ofthe probiotic microorganisms of about 97% of the initial value at theend of the small intestine on oral administration. It is thereforenecessary to provide a significantly larger amount of the probioticmicro-organisms in order to achieve adequately high activity.

DE 1937361 A1 describes an oral administration form comprising probioticmicro-organisms in which the loss of activity of the probioticmicroorganisms which is associated with the stomach-intestine passage isclaimed to be prevented by the use of a gastric juice-resistant coatingconsisting of shellac. It is disadvantageous in this administration formthat the dissolution of the coating material is dependent on a pluralityof physiological conditions, such as the intraluminal pH in thegastro-intestinal tract, the administration conditions (pre-,postprandial or with a meal), the composition of the meal, the age ofthe user, diseases, amount of liquid and the simultaneous administrationof medicaments, such as, for example, antacids. Furthermore, the use andprocessing of shellac is not unproblematical since shellac is a naturalproduct an, as a consequence of the natural variations in itscomposition associated therewith, is not always available in theconstant quality necessary for reproducible dissolution behaviour. Inthe case of increased moisture levels, sticking together can occur inthe case of shellac film tablets, meaning that the integrity of thecoating may be impaired. Compliance of the user and the efficacy of theprobiotic microorganisms are thus possibly not fully guaranteed.Furthermore, shellac can only be processed with organic solvents, whichresults in increased costs compared with processing of aqueous solutionsand may disadvantageously result in residues of organic solvents, whichare undesired from a toxicological point of view, remaining in theadministration form. In addition, the use of shellac as coating materialrequires larger amounts of a softening additive since shellac isunsuitable as coating material without the addition of softeners as aconsequence of its very high brittleness and fragility. However, theaddition of softeners is problematical since they may escape into theenvironment from the shellac film during storage of the finishedadministration form, impairing the properties of the coating andshortening the shelf life of the administration form. In addition,shellac “ages” during storage, i.e. the functional groups present in theshellac may react with one another and thus crosslink, which results ina slowing of the dissolution time of the shellac coating.

The object of the present invention was to provide an oraladministration form which liberates the probiotic microorganismsreproducibly in the human and/or animal intestine in order to ensure theactivity of the probiotic microorganisms and thus health-promotingaction thereof in the intestine. The oral administration form shouldfurthermore have a good shelf life and be simple and inexpensive toproduce.

Surprisingly, the object has been achieved by the provision of an oraladministration form which comprises at least one species of probioticmicroorganisms and which itself and/or in which the probioticmicroorganisms is/are provided with a coating which comprises at leasttwo cellulose ethers. The invention therefore relates to an oraladministration form comprising at least one species of probioticmicroorganisms which is characterised in that it itself and/or in whichthe probiotic microorganisms is/are provided with a coating whichcomprises at least two cellulose ethers.

The coating comprising at least two cellulose ethers can be applied fromaqueous solutions, meaning that residues of organic solvents canbasically be avoided. The addition of softeners in the coating canadvantageously be avoided, meaning that the storage stability is notimpaired thereby.

The oral administration form is preferably a tablet, a dragee, acapsule, a granular material, a pellet preparation or a powder,particularly preferably a tablet and very particularly preferably amultilayered tablet.

Suitable probiotic microorganisms are all microorganisms which eitherthemselves usually occur in the healthy human or animal body and have ahealth-promoting action on the healthy, unhealthy or diseased human oranimal body.

The probiotic microorganisms employed are preferably livingLactobacilli, Bifidobacteria and/or Streptococci. Particular preferenceis given to the species Lactobacillus casei, Lactobacillus acidophilus,Lactobacillus reuteri, Lactobacillus bifidum, Lactobacillus gasseri,Lactobacillus plantarum, Lactobacillus johnsonii, Lactobacillusrhamnosus, Lactobacillus fermentum, Lactobacillus paracasei,Lactobacillus crispatus, Bifidobacterium longum, Bifidobacteriumbifidum, Bifidobacterium longum, Bifidobacterium lactis, Bifidobacteriumbrevis, Bifidobacterium animalis, Bifidobacterium adolescentis,Bifidobacterium infantis, Streptococcus thermophilus and/or Lactococcuslactis.

The amount of the probiotic microorganisms in the oral administrationform according to the invention should be selected in such a way thatthe health-promoting action aimed at is ensured. The oral administrationform according to the invention preferably comprises 10³ to 10¹²,particularly preferably 10⁵ to 10¹¹ and very particularly preferably 10⁷to 10¹⁰ probiotic microorganisms. It is advantageous for the stabilitywith respect to the number and activity of living microorganisms if thematerials used, in particular the support material in which theprobiotic micro-organisms are embedded, have the lowest possible watercontent. The water content is preferably ≦3.0% by weight, particularlypreferably ≦0.1 % by weight, based on the weight of the supportmaterial.

The cellulose ethers present in the coating of the oral administrationform according to the invention are substances which are swellable orform a gel in aqueous media, where the swelling or gel formation takesplace to different extents and at different rates depending on the ethersubstituents present in the respective cellulose ether. The coating ofthe oral administration form according to the invention comprises atleast two cellulose ethers, each having different swelling orgel-formation behaviour, which are matched to one another in such a waythat the probiotic cultures present in the oral administration formaccording to the invention are released in a delayed manner in theintestine after the oral administration form has been taken by the useras a consequence of swelling and ultimately dissolution and/orstructural detachment of the coating. The delay in the release issubstantially independent of the respective pH conditions and is suchthat it corresponds to the time that the oral administration formrequires in order to pass through the stomach in substantially unchangedform and to reach the intestine after being taken by the user. Suitabledelay times for the oral administration form according to the inventionare those which increase the survival rate of the probioticmicroorganisms in the small intestine as far as the terminal ileum by atleast 5-fold compared with the uncoated administration form. Theduration of the delay is dependent on the type of cellulose etherspresent in the coating and can be adjusted to the desired value byvariation of the mixing ratios in which they are present with respect toone another and by variation of the layer thickness of the coating. Themixing ratios of the cellulose ethers to one another which are necessaryin each case for the desired release profile and the layer thicknesswhich is necessary in each case can be determined and optimised herewith reference to experiments in in-vitro models, for example theso-called TNO model (dynamic gastrointestinal model, as described inMarteau, P et al. (1997) Survial of Lactic Acid Bacteria in a DynamicModel of the Stomach and Small Intestine: Validation and the Effects ofBile, J Dairy Sci 80:1031-1037).

In general, a coating comprising two different cellulose etherscomprises the latter in a weight ratio of 0.1:99.9 to 99.9:0.1. Thelayer thickness of the coating is generally 0.5 to 20 mg per cm²,preferably 5 to 15 mg per cm².

According to an embodiment of the invention, the oral administrationform comprises in the coating cellulose ethers which contain, as ethersubstituents, hydroxyalkyl groups, preferably hydroxyethyl,hydroxypropyl and/or dihydroxypropyl groups, particularly preferablyhydroxypropyl groups. Cellulose ethers containing hydroxyalkyl groups asether substituents which can be employed for the invention areaccordingly, for example, hydroxyethylcellulose, hydroxypropylcelluloseand di-hydroxypropylcellulose.

According to a preferred embodiment of the invention, at least one ofthe cellulose ethers present in the coating of the oral administrationform also contains alkyl groups, preferably methyl and/or ethyl groups,particularly preferably methyl groups, as ether substituents besideshydroxyalkyl groups. Suitable cellulose ethers for the invention whichalso contain alkyl groups as ether substituents besides hydroxyalkylgroups are, for example, ethylhydroxyethylcellulose,hydroxypropylmethylcellulose, hydroxypropylethylcellulose andhydroxyethylmethylcellulose.

According to a particularly preferred embodiment of the invention, thecoating of the oral administration form according to the inventioncomprises one cellulose ether which contains exclusively hydroxyalkylgroups as ether substituents together with one cellulose ether whichalso contains alkyl groups as ether substituents besides hydroxyalkylgroups.

The oral administration form according to the invention veryparticularly preferably comprises hydroxypropylmethylcellulose andhydroxypropylcellulose as cellulose ethers in the coating.Hydroxypropylmethylcellulose and hydroxypropylcellulose may be presenthere in a weight ratio to one another of 90:10 to 10:90, preferably in aweight ratio to one another of 30:70 to 70:30, particularly preferablyin a weight ratio of about 35:65. Hydroxypropylmethylcellulose andhydroxypropylcellulose are preferably employed as a binary mixture.

The proportion by weight of the cellulose ethers present in the coating,based on the total weight of the oral administration form, is preferably1 to 20% by weight, particularly preferably 1.5 to 10% by weight andvery particularly preferably 3 to 5% by weight.

Besides the cellulose ethers mentioned, the coating may also, forexample in order to increase its physical stability, comprisealkylcellulose ethers, such as, for example, methylcellulose orethylcellulose. If alkylcellulose ethers are present, they arepreferably present in an amount of 0.5 to 10% by weight, based on thedry weight of the coating.

It is essential for the oral administration form according to theinvention that it is completely surrounded by the coating.

A further preferred embodiment of the oral administration form comprisesprobiotic microorganisms which are themselves provided with a gastricjuice-resistant coating. To this end, the probiotic microorganisms aredried by various methods known to the person skilled in the art andsubsequently provided with the coating.

The coating preferably does not comprise any further adjuvants. On aproduction scale, it may be helpful to employ a release agent.Preference is then given to the use of stearates, for example magnesiumstearate, glycerol monostearate, glyceryl dipalmitostearate or talc.Stearates may be present in a proportion by weight of 1 to 10% byweight, based on the dry weight of the coating, preference is given toabout 5% by weight of talc, based on the dry weight of the coating, in aproportion by weight of up to 100% by weight, preferably a proportion byweight of 30 to 50% by weight.

The coating can be applied from aqueous, organic or hydroalcoholicsolution. The coating is preferably applied from aqueous solution. Theinvention therefore also relates to a process for the production of theoral administration form according to the invention which ischaracterised in that the coating is applied from aqueous solutionand/or from organic solution, preferably from aqueous solution. In thecase of application of the coating by means of an organic solution, thisis preferably carried out from alcoholic solution, particularlypreferably from hydroalcoholic solution, i.e. from a mixture of waterand alcohol. The alcohol employed is preferably ethanol.

The coating can be applied by conventional methods known to the personskilled in the art, such as, for example, tablet coating, spraying ofsolutions, dispersions or suspensions, by melt methods or by powderapplication methods. The coating is preferably applied by means of adrum coater or by the fluidised-bed method, for example by the Wurstermethod.

The coatings appear clear to opaque. For colouring, coloured pigments,lakes or dyes can be added.

According to a preferred embodiment, the oral administration formaccording to the invention comprises further nutrition-relevantadditives in addition to the probiotic microorganisms. It preferablycomprises vitamins, mineral substances, trace elements, roughage,enzymes, plant extracts, proteins, carbohydrates and/or fats. If theoral administration form comprises nutrition-relevant additives whosedigestion already begins in the stomach, such as, for example, proteins,it is important that these nutrition-relevant additives are at leastincompletely surrounded by the coating.

Depending on the nutrition-relevant additives employed here, it may benecessary to incorporate them into the oral administration formaccording to the invention in such a way that they do not come intocontact with one another and/or with the probiotic microorganisms. Thisis preferably achieved by incorporation of the nutrition-relevantadditives and/or microorganisms into different layers of a multilayeredtablet.

Preferred vitamins are vitamin A (β-carotene), vitamin C, vitamin E,vitamins of the B complex and/or vitamin K. Particularly preferredvitamins are vitamin A, vitamin C and/or vitamin E. The amount ofvitamins generally depends on the recommended minimum required dose forthe respective vitamin, but this may also be exceeded by on average 50to 300%. Preferred ranges are between 50 and 300 mg for vitamin C, 10 to50 mg for vitamin E, ≦1.5 mg for vitamin A and 10 μg to 20 mg for thevitamins of the B complex.

Preferred mineral substances are inorganic or organic sodium, potassium,calcium, magnesium, zinc and/or iron salts which are suitable forconsumption, preferably in the form of carbonates, bicarbonates,phosphates, biphosphates, sulfates, bisulfates, chlorides, fluorides,citrates and/or lactates. The proportion of mineral substances, based onthe total weight of the oral administration form, is preferably from 20to 40% by weight. The oral administration form according to theinvention preferably comprises silicon, chromium, manganese, iodine,molybdenum and/or selenium as trace elements.

As roughage, the oral administration form according to the inventionpreferably comprises soya bran, maize bran, wheat bran and/or cerealwhole grain, particularly preferably soya bran. The proportion ofroughage, based on the total weight of the oral administration form, ispreferably 2 to 50% by weight.

Preferred enzymes or coenzymes are lipases and/or proteases or CoEnzymQ, superoxide dismutase and/or gluthathione peroxidase, which promotestomach and/or intestinal function and/or metabolism. These can beintroduced in an amount known per se and in a form known per se.

The oral administration form may additionally comprise further probioticsubstances, preferably oligofructose and/or other oligo sugars.

Preferred plant extracts are dry extracts and here in particular thosewhich comprise bioflavonoids, polyphenols, phytooestrogens and/orsaponins, such as, for example, from Echinaceae.

The oral administration form according to the invention preferablycomprises, as proteins, soya protein and/or milk protein and/or, asfats, fats which contain poly-unsaturated fatty acids.

The oral administration form according to the invention may additionallycomprise conventional adjuvants and additives, depending on theembodiment. The choice of adjuvants and/or additives also depends on thefood regulations of the country in which the oral administration formaccording to the invention is to be used. The adjuvants and/or additivesused, for example for the tablets, multilayered tablets and/or drageesaccording to the invention, are starch (for example corn starch), talc,microcrystalline cellulose, lactose, highly disperse silicon dioxide,polyvinyl-pyrrolidone and/or cellulose powder. Further constituentswhich can be employed as binders and/or release agents arecarbohydrates, such as, for example, mannitol, sorbitol, xylitol,glucose, sucrose, fructose, maltose, dextrose, maltodextrin and/orkaolin, and/or cellulose derivatives, such as, for example,methylcellulose, hydroxypropylcellulose and/orhydroxypropylmethylcellulose, and/or calcium carbonate, calciumstearate, magnesium stearate and/or glycerol stearate. The oraladministration form according to the invention may furthermore alsocomprise dyes, flavours and/or aromas, as well as lubricants,antioxidants and/or stabilisers. The content of these basic substancesdepends on the one hand on the target content of probioticmicroorganisms, vitamins, enzymes, roughage, etc. and on the other handon criteria which determine the mechanical-physical properties of theoral administration form, such as, for example, hardness,compressibility, size, colour and/or shape.

The oral administration form according to the invention can be producedby various methods known to the person skilled in the art. These methodsare disclosed, for example, in H. Sucker, P. Fuchs, P. Speiser,“Pharmazeutische Technologie” [Pharmaceutical Technology], Stuttgart1978 or K. H. Bauer, K. H. Frömming, C. Führer, “PharmazeutischeTechnologie” [Pharmaceutical Technology], Stuttgart 1986. They arehereby incorporated by way of reference and are thus part of thedisclosure.

The examples explain the invention without being restricted thereto.

EXAMPLE 1

A mixture of 45% of bacteria preparation, 28.7% of tricalcium phosphate,19% of microcrystalline cellulose, 2% of glyceryl palmitostearate, 0.6%of magnesium stearate and 4.7% of disintegrant was compressed togetherwith a vitamin and mineral substance mixture in an E. Hata rotary tabletpress to give a bean-shaped tablet having a core weight of 1.0 g and thedimensions 18.0 mm×8.0 mm×7.2 mm. A mixture of 35 parts ofhydroxypropylmethylcellulose and 65 parts of hydroxypropylcellulose wassubsequently sprayed on from aqueous solution in an O'Hara drum coaterwith a batch size of 15 kg. The amount of sprayed-onhydroxy-propylmethylcellulose/hydroxypropylcellulose mixture was 5% byweight, based on the weight of the core, corresponding to 11.74 mg percm² of tablet surface.

In an in-vitro experiment in the TNO model, the uncoated tablet coresare compared with the coated tablets from Example 1. The recovery fromthe initial value of 100% represents the survival rate of the probioticmicroorganisms after passing through the stomach and small intestinemodel.

Survival rate of Bifidobacteria Passage time (min) Tablet core Coatedtablet 360 2.3% 21.2%

EXAMPLE 2

A mixture of 65% of bacteria preparation, 20% of tricalcium phosphate,6% of microcrystalline cellulose, 2% of glyceryl palmitostearate, 0.6%of magnesium stearate and 6.4% of disintegrant was compressed togetherwith a vitamin and mineral substance mixture in a Fette rotary tabletpress to give a bean-shaped tablet having a core weight of 1.35 g andthe dimensions 21.0 mm×10.0 mm×8 mm. A mixture of 50 parts ofhydroxypropylmethylcellulose and 50 parts of hydroxypropylcellulose wassubsequently sprayed on from aqueous solution in an O'Hara drum coaterwith a batch size of 15 kg. The amount of sprayed-onhydroxy-propylmethylcellus/hydroxypropylcellulose mixture was 7% byweight, based on the weight of the core, corresponding to 17.42 mg percm² of tablet surface.

EXAMPLE 3

A mixture of 45% of bacteria preparation, 28.7% of tricalcium phosphate,19% of microcrystalline cellulose, 2% of glyceryl palmitostearate, 0.6%of magnesium stearate and 4.7% of disintegrant was compressed togetherwith a vitamin and mineral substance mixture in an E. Hata rotary tabletpress to give a bean-shaped tablet having a core weight of 1.0 g and thedimensions 18.0 mm×8.0 mm×7.2 mm. A mixture of 35 parts ofhydroxypropylmethylcellulose and 65 parts of hydroxypropylcellulose wassubsequently sprayed on from aqueous solution in a Pellegrini drumcoater with a stomach size of 250 kg. The amount of sprayed-onhydroxypropylmethylcellulose/hydroxypropylcellulose mixture was 5% byweight, based on the weight of the core, corresponding to 11.74 mg percm² of tablet surface.

In an in-vitro experiment in the TNO model, the uncoated tablet coresare compared with the coated tablets from Example 3. The recovery fromthe initial value of 100% represents the survival rate of the probioticmicroorganisms after passing through the stomach and small intestinemodel.

Survival rate of Lactobacillus Passage time (min) Tablet core Coatedtablet 360 1.6% 9.7%

EXAMPLE 4

A mixture of 65% of bacteria preparation, 20% of tricalcium phosphate,6% of microcrystalline cellulose, 2% of glyceryl palmitostearate, 0.6%of magnesium stearate and 6.4% of disintegrant was compressed togetherwith a vitamin and mineral substance mixture in a Fette rotary tabletpress to give a bean-shaped tablet having a core weight of 1.35 g andthe dimensions 21.0 mm×10.0 mm×8 mm. A mixture of 35 parts ofhydroxypropylmethylcellulose and 65 parts of hydroxypropylcellulose wassubsequently sprayed on from aqueous solution in an O'Hara drum coaterwith a stomach size of 15 kg. The amount of sprayed-onhydroxypropylmethylcellulose/hydroxypropylcellulose mixture was 7% byweight, based on the weight of the core, corresponding to 17.42 mg percm² of tablet surface.

EXAMPLE 5

A mixture of 45% of bacteria preparation, 28.7% of tricalcium phosphate,19% of microcrystalline cellulose, 2% of glyceryl palmitostearate, 0.6%of magnesium stearate and 4.7% of disintegrant was compressed togetherwith a vitamin and mineral substance mixture in an E. Hata rotary tabletpress to give a bean-shaped tablet having a core weight of 1.0 g and thedimensions 18.0 mm×8.0 mm×7.2 mm. A mixture of 35 parts ofhydroxypropylmethylcellulose and 65 parts of hydroxypropylcellulose wassubsequently dissolved in water, and 5% by weight of magnesium stearate,based on the polymer dry substance, were subsequently incorporated, andthe mixture was sprayed on in a Pellegrini drum coater with a stomachsize of 250 kg. The amount of sprayed-onhydroxypropylmethylcellulose/hydroxypropylcellulose mixture was 5% byweight, based on the weight of the core, corresponding to 11.74 mg percm² of tablet surface.

EXAMPLE 6

A mixture of 45% of bacteria preparation, 28.7% of tricalcium phosphate,19% of microcrystalline cellulose, 2% of glyceryl palmitostearate, 0.6%of magnesium stearate and 4.7% of disintegrant was compressed togetherwith a vitamin and mineral substance mixture in an E. Hata rotary tabletpress to give a bean-shaped tablet having a core weight of 1.0 g and thedimensions 18.0 mm×8.0 mm×7.2 mm. A mixture of 35 parts ofhydroxypropylmethylcellulose and 65 parts of hydroxypropylcellulose wassubsequently dissolved in an ethanol/water mixture (70 parts:30 parts),and 5% by weight of magnesium stearate, based on the polymer drysubstance, were subsequently incorporated, and the mixture was sprayedon in a Pellegrini drum coater with a stomach size of 333 kg. The amountof sprayed-on hydroxypropylmethylcellulose/hydroxypropylcellulosemixture was 7% by weight, based on the weight of the core, correspondingto 16.43 mg per cm² of tablet surface.

EXAMPLE 7

A mixture of 45% of bacteria preparation, 28.7% of tricalcium phosphate,19% of microcrystalline cellulose, 2% of glyceryl palmitostearate, 0.6%of magnesium stearate and 4.7% of disintegrant was compressed togetherwith a vitamin and mineral substance mixture in an E. Hata rotary tabletpress give a bean-shaped tablet having a core weight of 1.0 g and thedimensions 18.0 mm×8.0 mm×7.2 mm. A mixture of 35 parts ofhydroxypropylmethylcellulose and 60 parts of hydroxypropylcellulose and5 parts of hydroxyethylcellulose was subsequently sprayed on fromaqueous solution in a Bohle drum coater with a batch size of 5 kg. Theamount of sprayed-onhydroxypropylmethylcellulose/hydroxypropylcellulose/hydroxyethylcellulosemixture was 5% by weight, based on the weight of the core, correspondingto 11.74 mg per cm² of tablet surface.

EXAMPLE 8

A mixture of 9.8% of bacteria preparation, 35.0% of inulin, 28.7% oftricalcium phosphate, 18.9% of microcrystalline cellulose, 2.0% ofglyceryl palmitostearate, 0.6% of magnesium stearate and 5.0% ofdisintegrant was compressed together with a vitamin and mineralsubstance mixture in an E. Hata rotary tablet press to give abean-shaped tablet having a core weight of 1.0 g and the dimensions 18.0mm×8.0 mm×7.2 mm. A mixture of 65 parts of hydroxypropylmethylcelluloseand 35 parts of hydroxypropylcellulose was subsequently dissolved inwater, and 5% by weight of magnesium stearate, based on the polymer drysubstance, were subsequently incorporated, and the mixture was sprayedon in a Pellegrini drum coater with a batch size of 333 kg. The amountof sprayed-on hydroxypropyl-methylcellulose/hydroxypropylcellulosemixture was 5% by weight, based on the weight of the core, correspondingto 11.74 mg per cm² of tablet surface.

1. Oral administration form comprising at least one species of probioticmicroorganisms, characterised in that it itself and/or the probioticmicroorganisms is/are provided with a coating which comprises at leasttwo cellulose ethers.
 2. Oral administration form according to claim 1,characterised in that it is a tablet, a dragee, a capsule, a granularmaterial or a powder, preferably a tablet and particularly preferably amultilayered tablet.
 3. Oral administration form according to claim 1,characterised in that the probiotic microorganisms are Lactobacilli,Bifidobacteria and/or Streptococci, preferably Lactobacillus casei,Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus bifidum,Lactobacillus gasseri, Lactobacillus plantarum, Lactobacillus johnsonii,Lactobacillus rhamnosus, Lactobacillus fermentum, Lactobacillusparacasei, Lactobacillus crispatus, Bifidobacterium longum,Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium lactis,Bifidobacterium brevis, Bifidobacterium animalis, Bifidobacteriumadolescentis, Bifidobacterium infantis, Streptococcus thermophilusand/or Lactococcus lactis.
 4. Oral administration form according toclaim 1, characterised in that it comprises 103 to 1012 preferably 105to 1011 and particularly preferably 107 to 1010 probioticmicroorganisms.
 5. Oral administration form according to claim 1,characterised in that the cellulose ethers present in the coatingcontain hydroxyalkyl groups, preferably hydroxyethyl, hydroxypropyland/or dihydroxypropyl groups, particularly preferably hydroxypropylgroups, as ether substituents.
 6. Oral administration form according toclaim 5, characterised in that at least one of the cellulose etherspresent in the coating also contains alkyl groups, preferably methyland/or ethyl groups, particularly preferably methyl groups, as ethersubstituents besides hydroxyalkyl groups.
 7. Oral administration formaccording to claim 6, characterised in that the coating comprises acellulose ether which contains exclusively hydroxyalkyl groups as ethersubstituents together with a cellulose ether which also contains alkylgroups as ether substituents besides hydroxyalkyl groups.
 8. Oraladministration form according to claim 7, characterised in that thecellulose ethers present are hydroxypropylmethylcellulose andhydroxypropylcellulose.
 9. Oral administration form according to claim8, characterised in that the hydroxypropylmethylcellulose and thehydroxypropylcellulose are present in a weight ratio to one another of90:10 to 10:90, preferably in a weight ratio of 70:30 to 30:70,particularly preferably in a weight ratio of about 35:65.
 10. Oraladministration form according to claim 1, characterised in that itcomprises further nutrition-relevant additives, preferably vitamins,mineral substances, trace elements, roughage, enzymes, plant extracts,proteins, carbohydrates and/or fats.
 11. Process for the production ofan oral administration form according to claim 1, characterised in thatthe coating is applied from aqueous solution and/or from organicsolution, preferably from aqueous solution.